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@article{1353890,
author = {Kudová, Jana and Procházková, Jiřina and Vašiček, Ondřej and Perečko, Tomáš and Sedláčková, Miroslava and Pešl, Martin and Pacherník, Jiří and Kubala, Lukáš},
article_location = {San Francisco},
article_number = {6},
doi = {http://dx.doi.org/10.1371/journal.pone.0158358},
keywords = {INDUCIBLE FACTOR 1-ALPHA; GENE-EXPRESSION; CARDIAC DIFFERENTIATION; HIF-1-ALPHA; HEART; CARDIOMYOCYTES; MORPHOGENESIS; ENDODERM; ANGIOGENESIS; HIF-2-ALPHA},
language = {eng},
issn = {1932-6203},
journal = {Plos one},
title = {HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells},
volume = {11},
year = {2016}
}
TY - JOUR
ID - 1353890
AU - Kudová, Jana - Procházková, Jiřina - Vašiček, Ondřej - Perečko, Tomáš - Sedláčková, Miroslava - Pešl, Martin - Pacherník, Jiří - Kubala, Lukáš
PY - 2016
TI - HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells
JF - Plos one
VL - 11
IS - 6
SP - 1-17
EP - 1-17
PB - Public Library of Science
SN - 19326203
KW - INDUCIBLE FACTOR 1-ALPHA
KW - GENE-EXPRESSION
KW - CARDIAC DIFFERENTIATION
KW - HIF-1-ALPHA
KW - HEART
KW - CARDIOMYOCYTES
KW - MORPHOGENESIS
KW - ENDODERM
KW - ANGIOGENESIS
KW - HIF-2-ALPHA
N2 - Cardiac cell formation, cardiomyogenesis, is critically dependent on oxygen availability. It is known that hypoxia, a reduced oxygen level, modulates the in vitro differentiation of pluripotent cells into cardiomyocytes via hypoxia inducible factor-1alpha (HIF-1 alpha)-dependent mechanisms. However, the direct impact of HIF-1 alpha deficiency on the formation and maturation of cardiac-like cells derived from mouse embryonic stem cells (mESC) in vitro remains to be elucidated. In the present study, we demonstrated that HIF-1 alpha deficiency significantly altered the quality and quantity of mESC-derived cardiomyocytes. It was accompanied with lower mRNA and protein levels of cardiac cell specific markers (myosin heavy chains 6 and 7) and with a decreasing percentage of myosin heavy chain alpha and beta, and cardiac troponin T-positive cells. As to structural aspects of the differentiated cardiomyocytes, the localization of contractile proteins (cardiac troponin T, myosin heavy chain alpha and beta) and the organization of myofibrils were also different. Simultaneously, HIF-1 alpha deficiency was associated with a lower percentage of beating embryoid bodies. Interestingly, an observed alteration in the in vitro differentiation scheme of HIF-1 alpha deficient cells was accompanied with significantly lower expression of the endodermal marker (hepatic nuclear factor 4 alpha). These findings thus suggest that HIF-1 alpha deficiency attenuates spontaneous cardiomyogenesis through the negative regulation of endoderm development in mESC differentiating in vitro.
ER -
KUDOVÁ, Jana, Jiřina PROCHÁZKOVÁ, Ondřej VAŠIČEK, Tomáš PEREČKO, Miroslava SEDLÁČKOVÁ, Martin PEŠL, Jiří PACHERNÍK a Lukáš KUBALA. HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells. \textit{Plos one}. San Francisco: Public Library of Science, roč.~11, č.~6, s.~1-17. ISSN~1932-6203. doi:10.1371/journal.pone.0158358. 2016.
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